86 Older trials demonstrated significant improvements in anger for haloperidol, and suicidality for flupenthixol decanoate, as well as inconsistent effects on psychosis,36,72 irritability, and affective symptoms.22,72,77,78 Despite improvement with some

classical neuroleptics on individual symptoms, the antipsychotic class as a whole was associated with worsening overall severity of BPD in a recent meta-analysis.29 Classical neuroleptics may improve anger and impulsive aggression, but patients must be closely monitored for notable risks of extrapyramidal Inhibitors,research,lifescience,medical symptoms, tardive dyskinesia, and worsening overall functioning. Atypical antipsychotics are prescribed more often, due to greater tolerability Inhibitors,research,lifescience,medical and broader therapeutic benefits associated with serotonergic and noradrenergic activity beyond classical

neuroleptics’ stronger D2 receptor antagonism. Atypical antipsychotics are efficacious in the treatment of impulsive aggression.23-27 Across trials, this therapeutic effect is driven primarily by olanzapine and aripiprazole.31,43,44,87-93 These antipsychotics significantly improved affective instability, Inhibitors,research,lifescience,medical impulsivity, psychosis, and interpersonal dysfunction, leading to clinical consensus of breadth of efficacy in BPD.22,28 Despite one trial failing to establish statistically significant improvement with low-dose olanzapine,91 a larger, multisite sample recently showed significant but modest decreases in overall BPD severity,92 with further improvements seen in open-label continuation.93 Similarly broad benefits are seen in trials of Wnt activation aripiprazole improving impulsivity, Inhibitors,research,lifescience,medical aggression, affective instability, self-injury, and interpersonal symptoms.87-88 Aripiprazole has a long half-life and favorable metabolic profile,

which may contribute to ease in administration and effectiveness. The coordinated Inhibitors,research,lifescience,medical serotonergic and dopaminergic activity of aripiprazole as a partial agonist at D2 and 5-HT1A receptors, and antagonist at 5-HT2A receptors, may be more efficacious in treating impulsivity and aggression in BPD. Despite similar noradrenergic and serotonergic effects and favorable metabolic profile, ziprasidone has not proven efficacious in BPD.94 No studies have examined long-term risk versus Cell press benefit ratios associated with atypical antipsychotics in BPD. Dose ranges are typically lower than for primary psychotic disorders. Well-documented metabolic risks are associated particularly with olanzapine.22,29,43,47,89-93 The only benefit of polypharmacy elicited in one randomized controlled trial with BPD patients is lower risk of metabolic side effects when patients were administered the combination olanzapine-fluoxetine, relative to olanzapine alone.43 However, this effect has not been replicated sufficiently to recommend polypharmacy for this reason.